Exp Clin Endocrinol Diabetes 2012; 120(01): 1-6
DOI: 10.1055/s-0031-1285832
Review
© Georg Thieme Verlag KG Stuttgart · New York

Lifestyle and Genetics in Obesity and type 2 Diabetes

T. Temelkova-Kurktschiev
1   Medicobiological Unit, International Scientific Institute, National Sports Academy, , Bulgaria
2   Robert Koch German Medical Center, Sofia, Bulgaria
,
T. Stefanov
1   Medicobiological Unit, International Scientific Institute, National Sports Academy, , Bulgaria
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 29. April 2011
first decision 17. Juli 2011

accepted 21. Juli 2011

Publikationsdatum:
13. September 2011 (online)

Abstract

Obesity and type 2 diabetes mellitus are multifactorial health threats caused by a complex interplay between genetic predisposition and the environment with dramatically increasing worldwide prevalence. The role of heritability in their etiology is well recognized, however, the numerous attempts made in order certain genetic variants determining individual susceptibility to be identified have had limited success, until recently. At present the advancements in human genetics and the utilization of the genome-wide association approach have led to the identification of over 20 genetic loci associated with, respectively obesity and type 2 diabetes. Most of the genes identified to date, however, have modest effect on disease risk suggesting that both diseases are unlikely to develop without the individual being exposed to obesity- and/or type 2 diabetes-promoting environment. Indeed, unhealthy lifestyle, characterized by physical inactivity and food overconsumption is an unequivocally established risk factor for obesity and type 2 diabetes. Numerous epidemiological studies and randomized controlled trials, on the other hand, have demonstrated that lifestyle modification is effective in obesity and type 2 diabetes prevention. Furthermore, gene-lifestyle interaction studies suggest that genetic susceptibility to obesity and type 2 diabetes may be partially or totally kept under control by healthy lifestyle or lifestyle modification and that lifestyle determines whether an individual is likely to develop the disease. Inherited factors, however, seem to influence individual response to a lifestyle intervention program and even the motivation for lifestyle change. Personalized interventions according to genotype may be, therefore, considered in the future. By then lifestyle modification targeting dietary change and increased physical activity may be recommended for successful obesity and type 2 diabetes prevention irrespectively of genetic susceptibility.

 
  • References

  • 1 Ahmad T, Lee IM, Pare G et al. Lifestyle Interaction With Fat Mass and Obesity-Associated (FTO) Genotype and Risk of Obesity in Apparently Healthy U.S. Women. Diabetes Care 2011; 34: 675-680
  • 2 Allison DB, Kaprio J, Korkeila M et al. The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obes Relat Metab Disord 1996; 20: 501-506
  • 3 Andreasen CH, Stender-Petersen KL, Mogensen MS et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57: 95-101
  • 4 Barwell ND, Malkova D, Moran CN et al. Exercise training has greater effects on insulin sensitivity in daughters of patients with type 2 diabetes than in women with no family history of diabetes. Diabetologia 2008; 51: 1912-1919
  • 5 Bo S, Gambino R, Ciccone G et al. Effects of TCF7L2 polymorphisms on glucose values after a lifestyle intervention. Am J Clin Nutr 2009; 90: 1502-1508
  • 6 Brito EC, Lyssenko V, Renstrom F et al. Previously associated type 2 diabetes variants may interact with physical activity to modify the risk of impaired glucose regulation and type 2 diabetes: a study of 16 003 Swedish adults. Diabetes 2009; 58: 1411-1418
  • 7 Cai G, Cole SA, Butte N et al. A quantitative trait locus on chromosome 18q for physical activity and dietary intake in Hispanic children. Obesity (Silver Spring) 2006; 14: 1596-1604
  • 8 Ching PL, Willett WC, Rimm EB et al. Activity level and risk of overweight in male health professionals. Am J Public Health 1996; 86: 25-30
  • 9 Coakley EH, Rimm EB, Colditz G et al. Predictors of weight change in men: results from the Health Professionals Follow-up Study. Int J Obes Relat Metab Disord 1998; 22: 89-96
  • 10 Deeb SS, Fajas L, Nemoto M et al. Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 1998; 20: 284-287
  • 11 Eriksson KF, Lindgarde F. Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise. The 6-year Malmo feasibility study. Diabetologia 1991; 34: 891-898
  • 12 Eriksson KF, Lindgarde F. No excess 12-year mortality in men with impaired glucose tolerance who participated in the Malmo Preventive Trial with diet and exercise. Diabetologia 1998; 41: 1010-1016
  • 13 Farooqi IS, Keogh JM, Yeo GS et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348: 1085-1095
  • 14 Florez JC, Jablonski KA, Bayley N et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 2006; 355: 241-250
  • 15 Franks PW, Jablonski KA, Delahanty L et al. The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program. Diabetologia 2007; 50: 2451-2460
  • 16 Franks PW, Jablonski KA, Delahanty LM et al. Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program. Diabetologia 2008; 51: 2214-2223
  • 17 Haupt A, Thamer C, Heni M et al. Gene variants of TCF7L2 influence weight loss and body composition during lifestyle intervention in a population at risk for type 2 diabetes. Diabetes 2010; 59: 747-750
  • 18 Haupt A, Thamer C, Heni M et al. Impact of variation near MC4R on whole-body fat distribution, liver fat, and weight loss. Obesity (Silver Spring) 2009; 17: 1942-1945
  • 19 Haupt A, Thamer C, Machann J et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity (Silver Spring) 2008; 16: 1969-1972
  • 20 Haupt A, Thamer C, Staiger H et al. Variation in the FTO gene influences food intake but not energy expenditure. Exp Clin Endocrinol Diabetes 2009; 117: 194-197
  • 21 Herder C, Roden M. Genetics of type 2 diabetes: pathophysiologic and clinical relevance. Eur J Clin Invest 2010; 41: 679-692
  • 22 Hu FB, Li TY, Colditz GA et al. Television watching and other sedentary behaviors in relation to risk of obesity and type 2 diabetes mellitus in women. Jama 2003; 289: 1785-1791
  • 23 Hu FB, Sigal RJ, Rich-Edwards JW et al. Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study. Jama 1999; 282: 1433-1439
  • 24 Hu G, Qiao Q, Silventoinen K et al. Occupational, commuting, and leisure-time physical activity in relation to risk for Type 2 diabetes in middle-aged Finnish men and women. Diabetologia 2003; 46: 322-329
  • 25 International Obesity Taskforce Obesity the global epidemic. Available from http://www.iaso.org/iotf/obesity/obesitytheglobalepidemic/ cited 23 March 2011
  • 26 Kacerovsky-Bielesz G, Chmelik M, Ling C et al. Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes. Diabetes 2009; 58: 1333-1341
  • 27 Kaprio J, Tuomilehto J, Koskenvuo M et al. Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia 1992; 35: 1060-1067
  • 28 Kilpelainen TO, Lakka TA, Laaksonen DE et al. SNPs in PPARG associate with type 2 diabetes and interact with physical activity. Med Sci Sports Exerc 2008; 40: 25-33
  • 29 Knowler WC, Barrett-Connor E, Fowler SE et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403
  • 30 Knowler WC, Fowler SE, Hamman RF et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009; 374: 1677-1686
  • 31 Kosaka K, Noda M, Kuzuya T. Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males. Diabetes Res Clin Pract 2005; 67: 152-162
  • 32 Kriska AM, Saremi A, Hanson RL et al. Physical activity, obesity, and the incidence of type 2 diabetes in a high-risk population. Am J Epidemiol 2003; 158: 669-675
  • 33 Lappalainen TJ, Tolppanen AM, Kolehmainen M et al. The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study. Obesity (Silver Spring) 2009; 17: 832-836
  • 34 Leibel RL. Energy in, energy out, and the effects of obesity-related genes. N Engl J Med 2008; 359: 2603-2604
  • 35 Li G, Zhang P, Wang J et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet 2008; 371: 1783-1789
  • 36 Lindi VI, Uusitupa MI, Lindstrom J et al. Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes 2002; 51: 2581-2586
  • 37 Lindstrom J, Ilanne-Parikka P, Peltonen M et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 2006; 368: 1673-1679
  • 38 Lindstrom J, Louheranta A, Mannelin M et al. The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity. Diabetes Care 2003; 26: 3230-3236
  • 39 Manson JE, Greenland P, LaCroix AZ et al. Walking compared with vigorous exercise for the prevention of cardiovascular events in women. N Engl J Med 2002; 347: 716-725
  • 40 Martinez-Gonzalez MA, Martinez JA, Hu FB et al. Physical inactivity, sedentary lifestyle and obesity in the European Union. Int J Obes Relat Metab Disord 1999; 23: 1192-1201
  • 41 Medici F, Hawa M, Ianari A et al. Concordance rate for type II diabetes mellitus in monozygotic twins: actuarial analysis. Diabetologia 1999; 42: 146-150
  • 42 Meigs JB, Cupples LA, Wilson PW. Parental transmission of type 2 diabetes: the Framingham Offspring Study. Diabetes 2000; 49: 2201-2207
  • 43 Meisinger C, Lowel H, Thorand B et al. Leisure time physical activity and the risk of type 2 diabetes in men and women from the general population. The MONICA/KORA Augsburg Cohort Study. Diabetologia 2005; 48: 27-34
  • 44 Mekary RA, Feskanich D, Malspeis S et al. Physical activity patterns and prevention of weight gain in premenopausal women. Int J Obes (Lond) 2009; 33: 1039-1047
  • 45 Mitchell JA, Church TS, Rankinen T et al. FTO genotype and the weight loss benefits of moderate intensity exercise. Obesity (Silver Spring) 2010; 18: 641-643
  • 46 Montague CT, Farooqi IS, Whitehead JP et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903-908
  • 47 Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? 1962. Bull World Health Organ 1999; 77: 694-703 discussion 692–693
  • 48 Nelson TL, Fingerlin TE, Moss LK et al. Association of the peroxisome proliferator-activated receptor gamma gene with type 2 diabetes mellitus varies by physical activity among non-Hispanic whites from Colorado. Metabolism 2007; 56: 388-393
  • 49 Pan XR, Li GW, Hu YH et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20: 537-544
  • 50 Penn L, White M, Oldroyd J et al. Prevention of type 2 diabetes in adults with impaired glucose tolerance: the European Diabetes Prevention RCT in Newcastle upon Tyne, UK. BMC Public Health 2009; 9: 342
  • 51 Poulsen P, Kyvik KO, Vaag A et al. Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance – a population-based twin study. Diabetologia 1999; 42: 139-145
  • 52 Qi L, Cornelis MC, Zhang C et al. Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men. Am J Clin Nutr 2009; 89: 1453-1458
  • 53 Ramachandran A, Snehalatha C, Mary S et al. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 2006; 49: 289-297
  • 54 Rampersaud E, Mitchell BD, Pollin TI et al. Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 2008; 168: 1791-1797
  • 55 Rankinen T, Zuberi A, Chagnon YC et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 2006; 14: 529-644
  • 56 Razquin C, Martinez JA, Martinez-Gonzalez MA et al. A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes. Int J Obes (Lond) 2010; 34: 266-272
  • 57 Reinehr T, Friedel S, Mueller TD et al. Evidence for an influence of TCF7L2 polymorphism rs7903146 on insulin resistance and sensitivity indices in overweight children and adolescents during a lifestyle intervention. Int J Obes (Lond) 2008; 32: 1521-1524
  • 58 Rice T, Perusse L, Bouchard C et al. Familial aggregation of body mass index and subcutaneous fat measures in the longitudinal Quebec family study. Genet Epidemiol 1999; 16: 316-334
  • 59 Ruchat SM, Rankinen T, Weisnagel SJ et al. Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study. Diabetologia 2010; 53: 679-689
  • 60 Ruiz JR, Labayen I, Ortega FB et al. Attenuation of the effect of the FTO rs9939609 polymorphism on total and central body fat by physical activity in adolescents: the HELENA study. Arch Pediatr Adolesc Med 164: 328-333
  • 61 Sanake N, Sato J, Tsushita K et al. Prevention of type 2 diabetes in a primary healthcare setting: Three-year results of lifestyle intervention in Japanese subjects with impaired glucose tolerance. BMC Public Health 2011; 11: 40
  • 62 Schulze MB, Fung TT, Manson JE et al. Dietary patterns and changes in body weight in women. Obesity (Silver Spring) 2006; 14: 1444-1453
  • 63 Simonen RL, Perusse L, Rankinen T et al. Familial aggregation of physical activity levels in the Quebec Family Study. Med Sci Sports Exerc 2002; 34: 1137-1142
  • 64 Sjöström L, Narbro K, Sjöström CD et al. Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 23 (357) 741-752
  • 65 Speakman JR, Rance KA, Johnstone AM. Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring) 2008; 16: 1961-1965
  • 66 Stampfer MJ, Hu FB, Manson JE et al. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med 2000; 343: 16-22
  • 67 Stefan N, Thamer C, Staiger H et al. Genetic variations in PPARD and PPARGC1A Determine Mitochondrial Function and Change in Aerobic Physical Fitness and Insulin Sensitivity during Lifestyle Intervention. J Clin Endocrinol Metab 2007; 92: 1827-1833
  • 68 Stefanov TS, Vekova A, Kurktschiev D et al. Relationship of physical activity and eating behavior with obesity and type 2 diabetes mellitus: Sofia Lifestyle (SLS) study. Folia Medica 2011; 53: 11-18
  • 69 Stubbe JH, Boomsma DI, Vink JM et al. Genetic influences on exercise participation in 37 051 twin pairs from seven countries. PLoS One 2006; 1: e22
  • 70 Stunkard AJ, Sorensen TI, Hanis C et al. An adoption study of human obesity. N Engl J Med 1986; 314: 193-198
  • 71 Temelkova-Kurktschiev T, Hanefeld M, Chinetti G et al. Ala12Ala genotype of the peroxisome proliferator-activated receptor gamma2 protects against atherosclerosis. J Clin Endocrinol Metab 2004; 89: 4238-4242
  • 72 Teran-Garcia M, Rankinen T, Bouchard C. Genes, exercise, growth, and the sedentary, obese child. J Appl Physiol 2008; 105: 988-1001
  • 73 Thamer C, Machann J, Stefan N et al. Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. J Clin Endocrinol Metab 2008; 93: 1497-1500
  • 74 Timpson NJ, Emmett PM, Frayling TM et al. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr 2008; 88: 971-978
  • 75 Tuomilehto J, Lindstrom J, Eriksson JG et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343-1350
  • 76 Uusitupa M, Peltonen M, Lindström J et al. For the Finnish Diabetes Prevention Study Group. Ten-year mortality and cardiovascular morbidity in the Finnish diabetes prevention study – secondary analysis of the randomized trial. PLoS ONE 2009; 4: e5656
  • 77 van Dam RM, Rimm EB, Willett WC et al. Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med 2002; 136: 201-209
  • 78 Vaxillaire M, Froguel P. Genetic basis of maturity-onset diabetes of the young. Endocrinol Metab Clin North Am 2006; 35: 371-384 x
  • 79 Vimaleswaran KS, Li S, Zhao JH et al. Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene. Am J Clin Nutr 2009; 90: 425-428
  • 80 Vimaleswaran KS, Loos RJ. Progress in the genetics of common obesity and type 2 diabetes. Expert Rev Mol Med 2010; 12: e7
  • 81 Wang J, Kuusisto J, Vanttinen M et al. Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion. Diabetologia 2007; 50: 1192-1200
  • 82 Weyrich P, Machicao F, Reinhardt J et al. SIRT1 genetic variants associate with the metabolic response of Caucasians to a controlled lifestyle intervention – the TULIP Study. BMC Med Genet 2008; 9: 100
  • 83 Wild S, Roglic G, Green A et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047-1053
  • 84 Wing RR, Venditti E, Jakicic JM et al. Lifestyle intervention in overweight individuals with a family history of diabetes. Diabetes Care 1998; 21: 350-359